International Journal of Nanomedicine (Feb 2020)
Regulation of ERK1/2 and SMAD2/3 Pathways by Using Multi-Layered Electrospun PCL–Amnion Nanofibrous Membranes for the Prevention of Post-Surgical Tendon Adhesion
Abstract
Chunjie Liu, 1,* Siyu Tian, 2,* Jiangbo Bai, 2 Kunlun Yu, 2 Lei Liu, 3 Guoli Liu, 4 Ruiyi Dong, 5 Dehu Tian 2 1Department of Orthopedics, Tangshan Workers Hospital, Tangshan, Hebei 063000, People’s Republic of China; 2Department of Hand Surgery, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, People’s Republic of China; 3Department of Orthopedics, Changping District Hospital, Beijing 102200, People’s Republic of China; 4Department of Orthopedics, The Second Hospital of Tangshan, Tangshan, Hebei 063000,People’s Republic of China; 5Department of Orthopedics, Cangzhou Integrated Traditional Chinese and Western Medicine Hospital, Cangzhou, Hebei 061001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dehu TianDepartment of Hand Surgery, The Third Affiliated Hospital of Hebei Medical University, 139 Ziqiang Road, Shijiazhuang, Hebei 050017, People’s Republic of ChinaTel +86-151-3056-6366Fax +86-311-8860-3818Email [email protected]: Adhesion after tendon injury is a common complication in clinical practice. The lack of effective prevention mechanisms seriously affects the functional rehabilitation of patients. This research aimed to optimise the amniotic membrane and explain the mechanism of tendon–amniotic membrane by imitating the tendon sheath to construct a multilayer electrospun polycaprolactone (PCL) nanofibre membrane.Materials and Methods: Fresh amnions were subjected to freezing and vacuum drying. The two surfaces of freeze-dried amnions were coated with PCL nanofibres by electrospinning, thereby forming a multilayer composite membrane and constructing a growth factor-sustained release system conforming to the tendon-healing cycle. The new materials were characterised, and the biological effects on tenocytes and fibroblasts were evaluated. The tendon injury model of New Zealand rabbits was constructed to observe the effects on tendon adhesion and healing.Results: After freezing and vacuum drying, fresh amnions were found to effectively remove most of the cell components but retained the active components TGF-β 1, bFGF, VEGF, and PDGF, as well as the fibrous reticular structure of the basement membrane. After coating with PCL nanofibres, a composite membrane mimicking the structure of the tendon sheath was constructed, thereby strengthening the tensile strength of the amnion. By up-regulating the phosphorylation of ERK1/2 and SMAD2/3, the adhesion and proliferation of tenocytes and fibroblasts were promoted, and collagen synthesis was enhanced. In the rabbit tendon repair model, the composite membrane effectively isolated the exogenous adhesion tissue and promoted endogenous tendon healing.Conclusion: The composite membrane mimicking the structure of tendon sheath effectively isolated the exogenous adhesion tissue and achieved good tendon slip. By slowly releasing the growth factors TGF-β 1, bFGF, VEGF and PDGF, the ERK1/2 and SMAD2/3 pathways were regulated. Consequently, endogenous tendon healing was promoted. This strategy can alternatively address the clinical problem of tendon adhesion.Keywords: amniotic membrane, electrospinning, nanofibers, composite membrane, tendon adhesion
